Staff

Senescence in Vascular Regeneration

Objectives

Our goal is to prove that there is a causal relationship between senescence and the physiological degeneration of endothelial and vascular function in vitro and in vivo. As the signaling pathways that are responsible for the induction of senescence in endothelial cells are not fully unravelled yet, we further intend to investigate how senescence is induced in endothelial cells.

Our long term goals are:

To prove the causal relationship between senescence and endothelial dysfunction and cardio-vascular disease.

To show that strategies that interfere with senescence lead to endothelial and vascular regeneration.

To prove that inflammatory processes such as periodontitis trigger senescence and thereby lead to endothelial dysfunction and cardiovascular disease.

Research Focus

Accumulating evidence points towards an important role of senescence in aging, degeneration and for the response to certain injuries in vivo. The hypothesis is that senescence exhausts the reserves of somatic cells that are involved in cell-division and thereby cell-renewal - cellular skills indispensable for repair, integrity and regeneration. So far, no direct link between the presence of senescent cells and the onset of cardiovascular disease has been shown. Nevertheless, there are several observations suggesting senescence as mediator of or even the cause of cardiovascular complications. We intent to answer the question, whether known signaling pathways leading to cellular senescence play a role in the development of endothelial dysfunction and lead to cardiovascular disease. Overcoming senescence should lead to increased regenerative potential and result in improved endothelial and vascular function.

During the first funding period of the excellence cluster, we showed in cooperation with other REBIRTH groups that implementing regular physical exercise in sedentary middle aged man is associated with a rejuvenation of circulating leukocytes (significantly increased telomere length, telomerase activity and reduced p16INK4a expression) and may thereby improve their regenerative capacity. This was hampered in individuals with cardiovascular risk factors or suffering from severe periodontitis. Based on this observation and evidence from the literature that inflammatory processes induce senescence, we hypothesize that activation of senescence pathways could be the potential link between the inflammatory reactions induced by a chronic inflammatory process such as periodontitis and cardiovascular alterations. Exploration of this relationship is part of a DFG project that is linked to this REBIRTH project.